Middle aged CAMKII-Cre:CBSfl/fl mice: a new model for studying perioperative neurocognitive disorders

Zhen LI; Mengfan HE; Danqing DAI; Xiaofei GAO; Huazheng LIANG; Lize XIONG

doi:10.1538/expanim.23-0065

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Middle aged CAMKII-Cre:CBS^fl/fl mice: a new model for studying perioperative neurocognitive disorders

Zhen LI, Mengfan HE, Danqing DAI, Xiaofei GAO, Huazheng LIANG, Lize XIONG

著者情報

Zhen LI
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation
Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Mengfan HE
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation
Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Danqing DAI
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation
Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Xiaofei GAO
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation
Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Huazheng LIANG
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation
Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Monash Suzhou Research Institute
Lize XIONG
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation
Clinical Research Center for Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University
Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University

キーワード: anesthesia, animal model, cystathionine beta-synthase, perioperative neurocognitive disorders, surgery

ジャーナルオープンアクセス早期公開

論文ID: 23-0065

DOI https://doi.org/10.1538/expanim.23-0065

この記事には本公開記事があります。

The final version of this article is now available: Vol. 73 (2024), No. 1 pp. 109-123

詳細

抄録

Postoperative complications, such as perioperative neurocognitive disorders (PND), have become a major issue affecting surgical outcomes. However, the mechanism of PND remains unclear, and stable animal models of middle-aged PND are lacking. S-adenosylmethionine (SAM), a cystathionine beta-synthase (CBS) allosteric activator, can reduce the level of plasma homocysteine and prevent the occurrence of PND. However, the time and resource-intensive process of constructing models of PND in elderly animals have limited progress in PND research and innovative therapy development. The present study aimed to construct a stable PND model in middle-aged CAMKII-Cre:CBS^fl/fl mice whose CBS was specifically knocked out in CAMKII positive neurons. Behavioral tests showed that these middle-aged mice displayed cognitive deficits which were aggravated by exploratory laparotomy under isoflurane anesthesia. Compared with typical PND mice which were 18-month-old, these middle-aged mice showed similar cognitive deficits after undergoing exploratory laparotomy under isoflurane anesthesia. Though there was no significant difference in the number of neurons in either the hippocampus or the cortex, a significant increase in numbers of microglia and astrocytes in the hippocampus was observed. These indicate that middle-aged CAMKII-Cre:CBS^fl/fl mice can be used as a new PND model for mechanistic studies and therapy development for PND.

責任著者(Corresponding author)

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